Under normal circumstances, glucose is readily filtered by glomeruli and the filtered glucose is reabsorbed by the proximal tubule; essentially no glucose is normally excreted in the urine. However, the capacity for the proximal tubule to reabsorb glucose is limited; if the filtered load exceeds the proximal tubule's reabsorptive capacity, a portion of the filtered glucose will be excreted in the urine. Thus, elevated serum glucose concentrations (such as occur with diabetes mellitus) may result in an increase in filtered load of glucose and may overwhelm the tubules' reabsorptive capacity resulting in glucosuria.

Additionally, conditions which adversely affect proximal tubule function may also result in decreased reabsorption of glucose, and increased urinary glucose concentration, even in the presence of normal plasma glucose concentrations. Some of these conditions include Fanconi syndrome, Wilson's disease, hereditary glucosuria, and interstitial nephritis. These conditions are relatively rare, and most causes for elevated urine glucose concentrations are due to elevated serum glucose levels.